The purpose of this project is to study the role of the immune system in connective tissue metabolism. The collagen degrading enzyme, collagenase, can be produced by an immunologically competent cell population (macrophages). Prostaglandins have been shown to regulate the production of collagenase by these cells when stimulated by endotoxin. Thus, inhibition of the prostaglandin synthesizing enzyme eliminates collagenase production. This effect can be restored by the addition of exogenous prostaglandin. Other projects currently under investigation include: 1) hormonal regulation of prostaglandins, collagenase and the immune response; 2) the possible cellular defect(s) which may be responsible for the lack of bone resorption in osteopetrotic mice and rats. BIBLIOGRAPHIC REFERENCES: Rosenstreich, D.L., Glode, L.M., Wahl, L.M., Sandberg, A.L., and Mergenhagen, S.E.: Analysis of the cellular defect in mice unresponsive to endotoxin. In Schlesinger, D. (Ed.): Microbiology 1977, American Society of Microbiology, Washington, D.C. 1977. Wahl, L.M.: Hormonal regulation of macrophage collagenase activity. Biochem. Biophys. Res. Comm. 74: 838-845, 1977.